基于响应面法的甲磺酸二氢麦角碱缓释片释放度分析方法的开发

Development of an Analysis Method for the Release of Dihydroergotoxine Methanesulfonate Sustained Release Tablets Based on Response Surface Method

目的采用响应面法优化甲磺酸二氢麦角碱缓释片释放度的HPLC测定色谱条件。方法用单因素研究获得对响应值(分离度)影响较大的因素后,再以响应面法对相关参数进行优化,依据Box-Behnken中心组合实验设计原理,采用在三因素三水平对色谱条件的参数进行优化研究,对结果进行分析统计。结果建立色谱条件模型R=-0.17A^(2)-0.0005B^(2)-0.0099C^(2)-3.098×10^(-15) AB-0.004AC-0.001BC+0.52A+0.064B+0.939C-19.91。依据软件计算获得最佳试验参数,经试验检验,响应结果和软件计算结果基本一致,所得方法经方法学验证,专属性符合要求,线性范围为0.61~18.37μg·mL^(-1),线性回归方程为A=24403.6575C-4873.3249,相关系数r为0.9999,平均回收率为95.4%(RSD为0.66%),重复性的RSD为1.10%。结论依据软件计算获得最佳试验参数,经试验检验,响应结果和软件计算结果基本一致,所得方法经方法学验证,专属性符合要求。

OBJECTIVE The response surface method is used to optimize the analytical method in the determination of the dissolution of dihydroergotoxine methanesulfonate sustained release tablets,and the optimal chromatographic conditions are obtained by software calculation.METHODS After obtaining the factors that have a significant impact on the response value(resolution)through single factor research,the relevant parameters were optimized using response surface methodology.Based on the Box-Behnken central combination experimental design principle,the parameters of chromatographic conditions were optimized at three factors and three levels,and the results were analyzed and statistically analyzed.Result:A chromatographic condition model was established with R=-0.17A^(2)-0.0005B^(2)-00099C^(2)-3.098*10-15 A*B-0.004A*C-0.001B*C+0.52A+0.064B+0.939C-19.91.RESULTS Based on software calculation,the optimal experimental parameters were obtained.After experimental verification,the response results were basically consistent with the software calculation results.The obtained method was validated by methodology and its specificity met the requirements,with a linear range of 0.61~18.37μg/mL,the linear regression equation is A=24403.6575C-4873.3249,the correlation coefficient r is 0.9999,the average recovery rate is 95.4%(RSD is 0.66%),and the repeatability RSD is 1.10%.CONCLUSION Based on the software calculation,the optimal experimental parameters were obtained.After experimental verification,the response results were basically consistent with the software calculation results.The obtained method was validated by methodology and its specificity met the requirements.